Abstract

It is unknown whether MIRU-VNTR (Mycobacterial Interspersed Repetitive Unit-Variable Number of Tandem Repeat) is associated with drug resistance of Mycobacterium tuberculosis. The purpose of this study was to explore the ability of 24 MIRU loci to predict the drug resistance of Isoniazid (INH), Rifampicin (RFP), Streptomycin (SM), Ethambutol (EMB) and Pyrazinamide (PZA). We collected the drug resistance and MIRU loci information of 109 strains of M. tuberculosis from an open database. The results of multivariate logistic regression showed that the VNTR polymorphism of MTUB04 was related to INH resistance [odds ratio (OR) = 2.82, P = 0.00], RFP resistance (OR = 1.91, P = 0.02), SM resistance (OR = 1.98, P = 0.01) and EMB resistance (OR = 1.95, P = 0.03). MIRU40 was associated with INH resistance (OR = 2.22, P = 0.00). MTUB21 was connected with INH resistance (OR = 1.63, P = 0.02) and SM resistance (OR = 1.69, P = 0.01). MIRU26 was correlated with SM resistance (OR = 1.52, P = 0.04). MIRU39 was associated with EMB resistance (OR = 4.07, P = 0.02). The prediction power of MIRU loci were 0.84, 0.70, 0.85, and 0.74 respectively for INH (predicted by MTUB04, MIRU20, and MTUB21), RFP (predicted by MTUB04), SM (predicted by MTUB21 and MIRU26) and EMB (MTUB04 and MIRU39) through ROC analysis. Our results showed that MIRU loci were related to anti-tuberculosis drug and could predict the drug resistance of tuberculosis.

Highlights

  • Our results showed that MIRU loci were related to anti-tuberculosis drug and could predict the drug resistance of tuberculosis

  • According to the Global Tuberculosis Report 2013, 8.6 million people were infected with tuberculosis (TB), and 1.3 million people died from TB in 2012, and there were 3.6% of new cases and 20.0% of retreatment were infected with Multidrug-resistant TB (MDR-TB)1

  • Our study showed that anti-tuberculosis drug resistance (INH, RFP, SM, and EMB) were well correlated with MTUB04, MTUB21, MIRU26, MIRU39, and MIRU40

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Summary

Introduction

According to the Global Tuberculosis Report 2013, 8.6 million people were infected with tuberculosis (TB), and 1.3 million people died from TB in 2012, and there were 3.6% of new cases and 20.0% of retreatment were infected with Multidrug-resistant TB (MDR-TB). Environment (Lalor et al, 2013), including nutritional status, inadequacy of treatment and gene mutation were the main risk factors of drug-resistant tuberculosis. The efflux pump (Da Silva et al, 2011) and gene mutation (Nebenzahl-Guimaraes et al, 2014) have been widely used to explain the formation of anti-tuberculosis drug resistance. A recent study found that there was a correlation between genotypes of tuberculosis strains and drug-resistant tuberculosis (Liu et al, 2012). Mycobacterial interspersed repetitive unit-variable number of tandem repeat (MIRU-VNTR) method is widely used in genotyping the tuberculosis strains. The essence of MIRU (a total of 41, (Supply et al, 2000) in the tuberculosis) was a variable number tandem repeat, of which the number were highly polymorphic

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